Ricaurte G A, Martello A L, Katz J L, Martello M B
Department of Neurology, Francis Scott Key Medical Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
J Pharmacol Exp Ther. 1992 May;261(2):616-22.
The purpose of this study was to assess the duration of (+-)-3,4-methylenedioxymethamphetamine's (MDMA's) effects on serotonin containing neurons in nonhuman primates. Fifteen squirrel monkeys were used: three served as controls, 12 received MDMA s.c. at a dose of 5 mg/kg twice daily for 4 consecutive days. Two weeks, 10 weeks, 8 months and 18 months after drug treatment, groups (n = 3) of MDMA-treated monkeys, along with controls, were examined for regional brain content of serotonin and 5-hydroxyindoleacetic acid, and for the number of [3H] paroxetine-labeled serotonin uptake sites. Two weeks after MDMA treatment, monkeys showed profound reductions in all three serotonergic presynaptic markers. By 10 weeks, there was evidence of partial recovery in some brain regions (e.g., hippocampus, caudate nucleus, frontal cortex). However, by 18 months, it was evident that recovery did not continue, as serotonergic deficits returned to the level of severity observed 2 weeks after MDMA treatment. This was the case in all brain regions examined except the thalamus and hypothalamus. In the thalamus, the level of serotonin increased to 63% of control, whereas that of 5-hydroxyindoleacetic acid recovered completely. In the hypothalamus, concentrations of serotonin and 5-hydroxyindoleacetic acid were 140 and 187% of control, respectively. These results suggest that MDMA produces lasting effects on serotonergic neurons in nonhuman primates, with most brain regions showing evidence of persistent denervation and some showing signs of reinnervation (thalamus) or possibly even hyperinnervation (hypothalamus). The morphological and functional correlates of these enduring neurochemical changes in the MDMA-treated primate remain to be delineated.
本研究的目的是评估（±）-3,4-亚甲基二氧甲基苯丙胺（摇头丸）对非人灵长类动物含5-羟色胺神经元的作用持续时间。使用了15只松鼠猴：3只作为对照，12只连续4天每天两次皮下注射5mg/kg剂量的摇头丸。在药物治疗后2周、10周、8个月和18个月，对每组（n = 3）接受摇头丸治疗的猴子以及对照组进行检查，检测脑内5-羟色胺和5-羟吲哚乙酸的区域含量，以及[3H]帕罗西汀标记的5-羟色胺摄取位点的数量。摇头丸治疗后2周，猴子的所有三种5-羟色胺能突触前标记物均显著减少。到10周时，一些脑区（如海马体、尾状核、额叶皮质）有部分恢复的迹象。然而，到18个月时，很明显恢复并未持续，因为5-羟色胺能缺陷恢复到了摇头丸治疗后2周观察到的严重程度。除丘脑和下丘脑外，所有检查的脑区均是如此。在丘脑中，5-羟色胺水平升至对照的63%，而5-羟吲哚乙酸则完全恢复。在下丘脑中，5-羟色胺和5-羟吲哚乙酸的浓度分别为对照的140%和187%。这些结果表明，摇头丸对非人灵长类动物的5-羟色胺能神经元产生持久影响，大多数脑区显示出持续去神经支配的证据，一些脑区显示出再支配（丘脑）或甚至可能是超支配（下丘脑）的迹象。在接受摇头丸治疗的灵长类动物中，这些持久神经化学变化的形态学和功能相关性仍有待阐明。
